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CHAPTER 13
ANTIMICROBIAL THERAPY
CHAPTER OVERVIEW
One of the milestones of this century was the discovery of antibiotics. Prior to that time, as noted by
the medical writer Lewis Thomas, there was little chance of treating any of the serious microbial
diseases.
With the discovery of penicillin by Fleming, the era of microbial control was at hand. New
drugs were discovered and new chemicals synthesized. However, with every new conquest there is
also a danger. Antibiotic-resistant strains emerged and have continued to develop rapidly. Today we
are barely a step ahead. What new hopes and challenges will tomorrow bring?
The first part of this chapter presents the exciting development of antimicrobial therapy and
provides an interesting discussion of its general properties. How we determine microbial sensitivities
is also discussed. The second part is devoted to a complete description of the most important
antimicrobial agents, including those that affect the pathogenic fungi, viruses, protozoans, and
helminths. The chapter ends with a discussion of some of the problems that hospitals face in their
efforts to control the newly emerging resistant strains of bacteria.
CHAPTER OBJECTIVES
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Add these terms to your vocabulary: chemotherapy, chemotherapeutic agent, antimicrobial agent,
chemotherapeutic index, antibiosis, antibiotic, synthetic drug, and semisynthetic drug.
Explain how the first chemotherapeutic agents were developed, and summarize the subsequent
events in the development of chemotherapy.
Explain selective toxicity and spectrum of activity as these terms are applied to antimicrobial
agents.
List and describe five modes of action of antimicrobial agents.
List and describe three significant side effects associated with the use of antimicrobial agents.
Define the term resistance and describe several mechanisms by which microorganisms acquire
resistance to antibiotics.
List and describe three important methods used to determine sensitivities of microbes to
chemotherapeutic agents.
Identify six attributes of an ideal antimicrobial agent.
List the five modes of action of antibacterial agents, and describe the properties, uses, and side
effects of each.
Describe the properties, uses, and side effects of at least five types of antifungal agents; at least
five types of antiviral agents; at least four types of antiprotozoan agents; and at least two types of
antihelminthic agents.
Explain how resistant hospital infections arise and describe the problems associated with their
treatment and prevention.
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CHAPTER OUTLINE
I.
Antimicrobial Chemotherapy
A.
General features
B.
Terms
1.
Chemotherapy
2.
Chemotherapeutic agent
3.
Antimicrobial agents
4.
Antibiotics
5.
Synthetic drugs
6.
Semisynthetic drugs
II.
History of Chemotherapy
A.
Early history
B.
Ehrlich's contributions
C.
Domagk's discoveries and the development of sulfa drugs
D.
Fleming's discoveries
III.
General Properties of Antimicrobial Agents
A.
Selective toxicity
1.
Selective toxicity
2.
Therapeutic dosage level
3.
Chemotherapeutic index
B.
Spectrum of activity
1.
Broad spectrum
2.
Narrow spectrum
C.
Modes of action
1.
Inhibition of cell wall synthesis
2.
Disruption of cell membrane function
3.
Inhibition of protein synthesis
4.
Inhibition of nucleic acid synthesis
5.
Action as antimetabolites
a.
Competitive inhibition
b.
Molecular mimicry
D.
Kinds of side effects
1.
Toxicity
2.
Allergy
3.
Disruption of normal microbiota
E.
Resistance of microorganisms
1.
Definition
2.
How resistance is acquired
a.
Nongenetic resistance
b.
Genetic resistance
3.
Mechanisms of resistance
a.
Alteration of targets
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4.
5.
6.
b.
Alteration of membrane permeability
c.
Development of enzymes
d.
Alteration of an enzyme
e.
Alteration of a metabolic pathway
First, second, and third-line drugs
Cross-resistance
Limiting drug resistance
a.
Synergism
b.
Antagonism
IV.
Determination of Microbial Sensitivities to
Antimicrobial Agents
A.
Disk diffusion (Kirby-Bauer) methods
B.
Dilution methods
1.
Minimum inhibitory concentration
2.
Minimum bactericidal concentration
C.
Serum killing power
D.
Automated methods
V.
Attributes of an Ideal Antimicrobial Agent
A. Solubility in body fluids
B. Selective toxicity
C. Toxicity not easily altered
D. Nonallergenic
E.
Stability
F.
No Resistance
G.
Long shelf life
H.
Reasonable cost
VI.
Antibacterial Agents
A.
Sources of antibiotics
B.
Inhibitors of cell wall synthesis
1.
Penicillins
2.
Cephalosporins
3.
Other antibacterial agents that act on cell walls
C.
Disrupters of cell membranes
1.
Polymyxins
2.
Tyrocidins
D.
Inhibitors of protein synthesis
1.
Aminoglycosides
2.
Tetracyclines
3.
Chloramphenicol
4.
Other antibacterial agents that affect protein synthesis
a.
Macrolides
b.
Lincosamides
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E.
F.
VII.
Inhibitors of nucleic acid synthesis
1.
Rifampin
2.
Quinolones
Antimetabolites and other antibacterial agents
1.
Sulfonamides
2.
Isoniazid
3.
Ethambutol
4.
Nitrofurans
Antifungal Agents
A.
Imidazoles and triazoles
B.
Polyenes
1.
Amphotericin B
2.
Nystatin
C.
Griseofulvin
D.
Other antifungal agents
1.
Flucytosine
2.
Tolnaftate
3.
Terbinafine
VIII. Antiviral Agents
A.
Purine and pyrimidine analogues
1.
Idoxuridine and trifluridine
2.
Vidarabine
3.
Ribavirin
4.
Acyclovir
5.
Ganciclovir
6.
Zidovudine
B.
Amantadine
C.
Treatment of AIDS
D.
Interferon and immunoenhancers
1.
Levamisole
2.
Inosiplex
IX.
Antiprotozoan Agents
A.
Quinine
B.
Chloroquine and primaquine
C.
Metronidazole
D.
Other antiprotozoan agents
1.
Pyrimethamine
2.
Suramin sodium
X.
Antihelminthic Agents
A.
Niclosamide
B.
Mebendazole
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C.
XI.
Other antihelminthic agents
1.
Piperazine
2.
Ivermectin
Special Problems with Resistant Hospital Infections
A.
Development of resistance strains
B.
Problems of control
C.
Methods of treatment
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 Web Destinations
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http://www.cdc.gov/drugresistance/
This comprehensive web site at the CDC provides information about antibiotic resistance.
http://www.hopkins-abxguide.org/
This web site is an searchable antibiotic reference guide produced by the Johns Hopkins infectious
disease department
http://www.chiro.org/LINKS/FULL/Challenge_of_Antibiotic_Resistance.html
This site makes available a Scientific American article on bacterial resistance.
http://www.cellsalive.com/pen.htm
The Cells Alive! site offers numerous images of microbes and has a video clip of penicillin killing
a bacterium.
http://www.fda.gov/fdac/features/795_antibio.html This FDA site provides information and links
to antibiotic resistance topics and related subjects.
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